Title:White Matter Microstructure is Associated with Serum Clusterin and
Everyday Functioning in a Sample of Nondemented Older Adults
Volume: 18
Issue: 14
Author(s): Alexandra L. Clark, Seraphina K. Solders, Kelsey R. Thomas and Katherine J. Bangen*
Affiliation:
- Research Services, VA San Diego Healthcare System (VASDHS), San Diego, CA, USA
Keywords:
Mild cognitive impairment, serum clusterin, DTI, white matter hyperintensities, white matter microstructure, neurodegenerative disorder.
Abstract:
Background: Although clusterin-a protein involved in lipid metabolism, amyloid beta
clearance, and myelination-has been linked to gray matter atrophy within samples of older adults at
risk for Alzheimer’s disease, research exploring associations with white matter (WM) micro- and
macro- structural markers are largely limited.
Objective: The current study explored associations between serum clusterin protein levels and WM
micro- and macro- structural markers, and clarified whether variations in WM fractional anisotropy
(FA) were associated with functional abilities within in a racially homogenous sample of relatively
well-educated older adults free of dementia.
Methods: Participants underwent magnetic resonance imaging (MRI) brain exams and a blood
draw and completed a performance-based measure of everyday functioning. Multiple linear regression
adjusting for age, sex, APOE e4 positivity, and vascular risk were used to explore serum clusterin
associations with WM metrics, as well clarify potential links between WM microstructure and
everyday functioning.
Results: Higher serum clusterin was associated with lower FA in several thalamocortical (anterior
and posterior internal capsule, posterior thalamic radiation; ßs = -.32 to -.37, ps = .01 to .02) and association
fiber tracts (external capsule, superior longitudinal fasciculus; ßs = -.32 to -.40, ps = .02).
Serum clusterin was not associated with white matter hyperintensity volume (ß = .14, p = .28), but
higher FA of several WM tracts was associated with better performance on the Independent Living
Scale (ßs = .37 to .53, ps = .006 to .03).
Conclusions: Serum clusterin is differentially associated with WM metrics, and WM microstructure
is associated with everyday functioning.
